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[Cancer Research 62, 5129-5133, September 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Direct Association of TSLC1 and DAL-1, Two Distinct Tumor Suppressor Proteins in Lung Cancer1

Mika Yageta, Masami Kuramochi, Mari Masuda, Takeshi Fukami, Hiroshi Fukuhara, Tomoko Maruyama, Masabumi Shibuya and Yoshinori Murakami2

Tumor Suppression & Functional Genomics Project, National Cancer Center Research Institute, Tokyo 104-0045 [M. Y., M. K., M. M., T. F., H. F., T. M., Y. M.], and Department of Genetics, Institute of Medical Science, University of Tokyo, Tokyo 108-0071 [M. Y., M. S.], Japan

The tumor suppressor gene TSLC1, which we recently identified in human non-small cell lung cancer, encodes a membrane glycoprotein of the immunoglobulin superfamily. Here, we report that TSLC1 directly associates with DAL-1, a gene product of another lung tumor suppressor belonging to the protein 4.1 family. TSLC1 additionally interacts with the actin filament through DAL-1 at the cell-cell attached site where the complex formation of TSLC1 and DAL-1 is dependent on the integrity of actin cytoskeleton. Redistribution of both TSLC1 and DAL-1 to the newly generated membrane ruffling areas suggests that these proteins are also involved in cell motility accompanying the actin rearrangement. Furthermore, restoration of TSLC1 expression strongly suppressed the metastasis of a human non-small cell lung cancer cell line, A549, from the spleen to the liver in nude mice. These findings, together with frequent loss of their expression in lung cancers, suggest that TSLC1 and DAL-1 play a critical role in the same pathway involved in the suppression of lung tumor formation and metastasis.




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Copyright © 2002 by the American Association for Cancer Research.